A new method for the synthesis of neoglycopeptides.
A new method for conjugation of small carbohydrates to peptides based on maleimido-thiol chemistry is described. The reducing carbohydrate is reacted with S-trityl-2-mercaptoethylamine in methanol. The resulting Schiff base is then stabilized by acetylation with acetic anhydride to give an S-trityl-protected glycosylamide. Activation of the carbohydrate is effected by brief treatment with trifluoroacetic acid/triisopropylsilane, followed by precipitation in ether. The thiol-functionalized carbohydrate is then reacted with a maleimido-modified peptide to give a neoglycopeptide. The potential of this method was investigated using maltose as the model compound. Furthermore, we prepared five maleimido-modified model peptides. In contrast to some literature reports, we found that the maleimido group is stable to treatment trifluoroacetic acid/triisopropylsilane which was used to cleave the modified peptides from the resin.
Hansen
P R
PR
Chemistry Department, Royal Veterinary and Agricultural University, Frederiksberg, Denmark. prh@pepsyn.chem.kvl.dk
Olsen
C E
CE
Holm
A
A
D000107:Acetylation; D000595:Amino Acid Sequence; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006020:Glycopeptides / Q000138:chemical synthesis*; D008301:Maleimides / Q000737:chemistry; D008320:Maltose / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D012545:Schiff Bases; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014269:Trifluoroacetic Acid
D006020:Glycopeptides; D008301:Maleimides; D010455:Peptides; D012545:Schiff Bases; D013438:Sulfhydryl Compounds; D008320:Maltose; D014269:Trifluoroacetic Acid